Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits. Whole genome sequence data were generated for four affected individuals. No rare variants (MAF < 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G > A; p.(Glu112Lys), which is predicted to be damaging, segregated with disease. SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. Interestingly, SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Therefore, we performed immunohistochemistry to compare SPARCL1 and decorin localisation in corneal tissue from an affected family member and an unaffected control. Strikingly, the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. In summary, we describe a novel autosomal dominant corneal stromal dystrophy associated with a missense variant in SPARCL1, extending the phenotypic and genetic heterogeneity of inherited corneal disease.

Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias.

Preclinical data have confirmed that human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) can remuscularize the injured or diseased heart, with several clinical trials now in planning or recruitment stages. However, because ventricular arrhythmias represent a complication following engraftment of intramyocardially injected PSC-CMs, it is necessary to provide treatment strategies to control or prevent engraftment arrhythmias (EAs). Here, we show in a porcine model of myocardial infarction and PSC-CM transplantation that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. Two unique surface marker signatures, signal regulatory protein α (SIRPA)+CD90-CD200+ and SIRPA+CD90-CD200-, identify arrhythmogenic and non-arrhythmogenic cardiomyocytes, respectively. Our data suggest that modifications to current PSC-CM-production and/or PSC-CM-selection protocols could potentially prevent EAs. We further show that pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias.

Comprehensive Shielding System Enhances Radiation Protection for Structural Heart Procedures.

Background: This study of radiation exposure (RE) to physicians performing structural heart procedures evaluated the efficacy of a novel comprehensive radiation shield compared to those of traditional shielding methods. A novel comprehensive shielding system (Protego, Image Diagnostics Inc) has been documented to provide superior RE protection during coronary procedures compared to that provided by a standard "drop down" shield. The purpose of this study was to assess the efficacy of this shield in transcatheter aortic valve replacement (TAVR) procedures, which are associated with disproportionate RE to operators. Methods: This single-center, 2-group cohort, observational analysis compared RE to the primary physician operator performing TAVR using the Protego shield (n = 25) with that using a standard drop-down shield with personal leaded apparel (n = 25). RE was measured at both thyroid and waist levels with a real-time dosimetry system (RaySafe i3, RaySafe) and was calculated on a mean per case basis. Data were collected on additional procedural parameters, including access site(s) for device implantation, per case fluoroscopy time, air kerma, and patient factors, including body mass index. Between-group comparisons were conducted to evaluate RE by group and measurement sites. Results: The Protego system reduced operator RE by 99% compared to that using standard protection. RE was significantly lower at both the thyroid level (0.08 ± 0.27 vs 79.2 ± 62.4 µSv; P < .001) and the waist level (0.70 ± 1.50 vs 162.0 ± 91.0 µSv, P < .001). "Zero" total RE was documented by RaySafe in 60% (n = 15) of TAVR cases using Protego. In contrast, standard protection did not achieve zero exposure in a single case. Conclusions: The Protego shield system provides superior operator RE protection during TAVR procedures. This shield allows operators to work without the need for personal lead aprons and has potential to reduce catheterization laboratory occupational health hazards.

In Defense of Normothermic Regional Perfusion.

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an "all things considered" view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States.

Effects of a Brief Safe Drinking Intervention on Depressive and Anxiety Symptomatology: Examining Potential Side Effects of Deviance Regulation Theory Interventions.

College students are at a heightened risk of experiencing depression and anxiety symptomatology and engaging in maladaptive alcohol use. Understanding how alcohol interventions impact emotional functioning is essential. One such intervention uses Deviance Regulation Theory (DRT), which posits that behavior can be modified using targeted messaging as a function of perceived norms. DRT has been shown to be effective at increasing responsible drinking behaviors and decreasing alcohol-related consequences. However, it is unclear if this intervention influences emotional functioning. The current examines the impact of a DRT intervention on emotional functioning. Participants (n = 147) were recruited from a large Southeastern university. The study included a screening phase, intervention, and six-week follow-up. Participants were randomly assigned to one of three conditions: a positive message condition about people who drink responsibly, a negative message condition about people who do not drink responsibly, and an active control condition. During the study, all participants reported on depression/anxiety symptoms, alcohol use, responsible drinking, and alcohol-related consequences. Mixed-effects regression was used to analyze the data. Results suggest an overall reduction of depressive and anxiety symptomatology in the intervention conditions but not in the control condition. In the positive condition, there was a decrease in depressive and anxiety symptomatology. The messaging was not moderated by normative beliefs. The negative condition also led to decreases in depression and anxiety symptomatology over time. In addition, perceived norms moderated the negative message in the first week after the intervention, an effect consistent with DRT. Prior research indicates this intervention is efficacious for the reduction of adverse alcohol outcomes; these data show that the intervention may also have positive effects on downstream mental health outcomes.

Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS).

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

Diminishing warming effects on plant phenology over time.

Plant phenology, the timing of recurrent biological events, shows key and complex response to climate warming, with consequences for ecosystem functions and services. A key challenge for predicting plant phenology under future climates is to determine whether the phenological changes will persist with more intensive and long-term warming. Here, we conducted a meta-analysis of 103 experimental warming studies around the globe to investigate the responses of four phenophases - leaf-out, first flowering, last flowering, and leaf coloring. We showed that warming advanced leaf-out and flowering but delayed leaf coloring across herbaceous and woody plants. As the magnitude of warming increased, the response of most plant phenophases gradually leveled off for herbaceous plants, while phenology responded in proportion to warming in woody plants. We also found that the experimental effects of warming on plant phenology diminished over time across all phenophases. Specifically, the rate of changes in first flowering for herbaceous species, as well as leaf-out and leaf coloring for woody species, decreased as the experimental duration extended. Together, these results suggest that the real-world impact of global warming on plant phenology will diminish over time as temperatures continue to increase.

Predictors of spontaneous intracerebral hemorrhage mortality: a community-based study in Brno, Czech Republic.

BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage (ICH) is a serious medical condition with high mortality. However, factors leading to long-term mortality after ICH are largely unclear. The aim of this community-based study is to assess predictors of long-term mortality after spontaneous ICH. METHODS: We identified all patients admitted with spontaneous ICH to hospitals with a certified stroke unit in Brno, the second largest city in the Czech Republic (CR), in 2011, the year of the Czech Population and Housing Census. We reviewed their medical records for risk factors, radiographic parameters, and measures of post-stroke neurological deficit [National Institutes of Health Stroke Scale (NIHSS)]. Using the dates of death from the Czech National Mortality Register, we calculated mortality at 30 days, six months, one year, and three years after the ICH. Multivariate analysis with forward stepwise logistic regression was performed to determine independent predictors of mortality (p < 0.05). RESULTS: In 2011, 1086 patients with stroke were admitted to the four stroke-certified hospitals in Brno, CR. Of these, 134 had spontaneous ICH, with complete data available in 93 of them entering the final analysis. The mortality at 30 days, 6 months, 1 year, and 3 years post-ICH was 34%, 47%, 51%, and 63%, respectively. The mortality was highest in the first few days post-event, with 50% of patients dying in 255 days and average survival being 884 ± 90 days. Both NIHSS and modified ICH (MICH) score showed to be strong and reliable predictors of short- as well as long-term mortality; the risk of death post-ICH increased with older age and size of ICH. Other risk factors contributing to higher, primarily shorter-term mortality included history of cardiac failure, myocardial infarction, or atrial fibrillation. CONCLUSIONS: In our community-based study, we found that severity of neurological deficit at admission (NIHSS), combined with age and size of ICH, well predicted short- as well as long-term mortality after spontaneous ICH. A history of cardiac failure, myocardial infarction, or atrial fibrillation at presentation were also predictors of mortality, underscoring the need for optimal cardiac management in patients with ICH.

Mortality Rate of COVID-19 With Comorbid Pneumonia in a Rural Area.

BACKGROUND: A myriad of risk factors and comorbidities have been determined to influence COVID-19 mortality rates; among these is pneumonia. This study considers pneumonia as a risk factor for increased mortality in patients admitted with COVID-19 in a rural healthcare system. We predicted that the presence of pneumonia of any kind would increase mortality rates in patients admitted with COVID-19. METHODS: A retrospective observational study was conducted using data collected from hospitals in the Freeman Health System (FHS) located in Joplin and Neosho, Missouri. Data were collected between April 1, 2020, and December 31, 2021. Using International Classification of Diseases, Tenth Revision (ICD-10) codes, the investigators identified five distinct patient populations: patients with COVID-19 and pneumonia due to COVID-19 (P1); patients with COVID-19 but without pneumonia due to COVID-19 (P2); patients with COVID-19 and any type of pneumonia (P3); patients with COVID-19 but without any type of pneumonia (P4); and patients without COVID-19 and with any type of pneumonia (P5). In order to understand how pneumonia influences COVID-19 outcomes, the investigators used Wald's method and a two-sample proportion summary hypothesis test to determine the confidence interval and to compare the mortality rates between these populations, respectively. RESULTS: The population of patients with COVID-19 and any type of pneumonia (P3) and the population of patients with COVID-19 and pneumonia due to COVID-19 (P1) showed the highest mortality rates. The population of patients with COVID-19 but without any type of pneumonia (P4) had the lowest mortality rate. The data revealed that having pneumonia combined with COVID-19 in any patient population led to a higher mortality rate than COVID-19 alone. CONCLUSION: Mortality rates were higher among COVID-19 patients with pneumonia compared to COVID-19 patients without pneumonia. Additionally, pneumonia, by itself, was found to have a higher mortality rate compared to COVID-19 alone.

Clinical characteristics and functioning of adults with bipolar I disorder: Evidence from the mental and substance use disorders prevalence study.

BACKGROUND: Knowledge of clinical, treatment and life circumstances of individuals with bipolar I disorder (BP-I) in US households is informed by decades old epidemiological surveys. METHODS: The Mental and Substance Use Disorders Prevalence Study was conducted October 2020-October 2022. Clinicians administered the Structured Clinical Interview for the DSM-5 diagnosing 12-month prevalence of BP-I and other mental health disorders (MHD) among 4764 adults aged 18-65 years and collected sociodemographic information. We examined clinical characteristics, differences by sex and age among adults with BP-I, and compared adults with BP-I versus no MHD regarding sociodemographic characteristics, functioning, and substance use disorders (SUDs). RESULTS: Prevalence of BP-I in the MDPS was 1.5 %. Among those with BP-I, 73.4 % had comorbid psychiatric disorders, and 43.4 % had comorbid SUDs. Alcohol use disorder was higher in those with BP-I versus no MHD (33.0 % vs. 6.3 %). Mean Global Assessment of Functioning scores were lower among those with BP-I versus no MHD (53.2 vs. 77.0). Of individuals with BP-I, 64.9 % had past-year outpatient, 5.4 % inpatient, and 18.7 % minimally adequate treatment (≥1 antimanic agent and ≥ 4 outpatient visits). Individuals with BP-I were less likely to be employed (37.3 % vs. 63.0 %) and have a family income ≥$20,000 (48.2 % vs. 81.9 %) versus no MDPS MHD. LIMITATIONS: The survey response rate was low. CONCLUSIONS: In this sample, many individuals with BP-I had psychiatric and SUD comorbidities, lived in poverty and had functional impairment. Few received adequate treatment; women and younger individuals were particularly disadvantaged. Early detection and treatment represent substantial opportunities to improve outcomes.

Severe Hyponatremia Secondary to Pituitary Macroadenoma With Internal Hemorrhage in the Postpartum Period: A Case Report.

Pituitary macroadenomas, especially those complicated by internal hemorrhage (pituitary apoplexy), can lead to severe endocrine dysfunction and visual disturbances. This is particularly challenging to diagnose in the postpartum period due to physiological changes associated with childbirth and breastfeeding. This case report aims to highlight the diagnostic and therapeutic complexities of managing severe hyponatremia and visual changes in a woman with a pituitary macroadenoma in the postpartum period.A 34-year-old female, five months postpartum, presented with a one-month history of intermittent nausea, headaches, and blurry vision, which worsened over the past week. Initial laboratory results revealed severe hyponatremia with a sodium level of 112 mEq/L. Imaging studies, including MRI, confirmed a 1.9 x 1.8 x 1.7 cm pituitary macroadenoma with internal hemorrhage exerting mass effect on the optic chiasm. The patient was managed with hypertonic saline for hyponatremia and empiric glucocorticoid supplementation for suspected adrenal insufficiency. A multidisciplinary approach involving endocrinology, neurosurgery, and ophthalmology was employed to address her complex medical needs. This case underscores the importance of considering pituitary pathology in women presenting with severe hyponatremia and visual changes postpartum. A multidisciplinary approach is essential for optimal management and prevention of long-term complications. Early recognition and appropriate intervention are crucial in ensuring a favorable outcome.

Electroactive Molecularly Imprinted Polymer Nanoparticles (eMIPs) for Label-free Detection of Glucose: Toward Wearable Monitoring.

The diagnosis of diabetes mellitus (DM) affecting 537 million adults worldwide relies on invasive and costly enzymatic methods that have limited stability. Electroactive polypyrrole (PPy)-based molecularly imprinted polymer nanoparticles (eMIPs) have been developed that rival the affinity of enzymes whilst being low-cost, highly robust, and facile to produce. By drop-casting eMIPs onto low-cost disposable screen-printed electrodes (SPEs), sensors have been manufactured that can electrochemically detect glucose in a wide dynamic range (1 µm-10 mm) with a limit of detection (LOD) of 26 nm. The eMIPs sensors exhibit no cross reactivity to similar compounds and negligible glucose binding to non-imprinted polymeric nanoparticles (eNIPs). Measurements of serum samples of diabetic patients demonstrate excellent correlation (>0.93) between these eMIPs sensor and the current gold standard Roche blood analyzer test. Finally, the eMIPs sensors are highly durable and reproducible (storage >12 months), showcasing excellent robustness and thermal and chemical stability. Proof-of-application is provided via measuring glucose using these eMIPs sensor in a two-electrode configuration in spiked artificial interstitial fluid (AISF), highlighting its potential for non-invasive wearable monitoring. Due to the versatility of the eMIPs that can be adapted to virtually any target, this platform technology holds high promise for sustainable healthcare applications via providing rapid detection, low-cost, and inherent robustness.

Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers.

The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies. The digital pathology prostate cancer atlas when used in conjunction with the biomarkers, will assist pathologists to accurately grade prostate cancer tissue samples.

The genetics of phenotypic plasticity. XVIII. Developmental limits restrict adaptive plasticity.

After environmental change, the trait evolution needed to rescue a population depends on the functional form of the plastic change (reaction norm) of that trait. Nearly all previous models of plasticity evolution for continuous traits have assumed that the functional form is linear, i.e., no limits on the range of plasticity. This paper examines the effect of developmental limits, modeled as a sigmoidal reaction norm, on evolutionary rescue after an abrupt environmental change and the subsequent evolution of plasticity, including genetic assimilation. We examined four different scenarios: (1) developmental limits only, (2) developmental limits plus a cost of plasticity, (3) developmental limits with developmental noise, and (4) developmental limits plus environmental variation. The probability of evolutionary rescue increased with an increase in phenotypic variation allowed by plastic development. With a smaller limit to the range of the plastic phenotype, the evolution of adaptive plasticity was limited, meaning the evolution of non-plastic genes was necessary. The addition of developmental constraints to the model did not speed up genetic assimilation, suggesting new theory is needed to understand empirical observations. The modeling framework presented here could be extended to different ecological and evolutionary conditions, alternative reaction norm shapes, the evolution of additional reaction norm parameters such as the range or the location of the inflection point on the environmental axis, or other function-valued traits.

Technical Feasibility and Safety of Image-Guided Biphasic Monopolar Pulsed Electric Field Ablation of Metastatic and Primary Malignancies.

PURPOSE: To assess the technical feasibility and safety of image-guided percutaneous biphasic monopolar pulsed electric field (PEF) ablation of primary and metastatic tumors. METHODS AND METHODS: With IRB approval and HIPAA compliance, this retrospective, single-institution study cohort of 17 patients (mean age: 53.5 years, range: 20 - 94 years) with overall progressive disease underwent 26 PEF ablation procedures for 30 metastatic (90%) and primary (10%) target lesions in the thorax (n=20), abdomen (n=7), and head and neck (n=3). Concurrent systemic therapy was used in 14/17 patients (82%). Follow-up imaging was scheduled for 1, 3, and 6 months after PEF ablation, and target and off-target lesion sizes were recorded. The overall response was assessed by the RECIST 1.1 criteria with imaging immediately before PEF serving as baseline. Adverse events (AEs) were determined by the Society of Interventional Radiology classification. RESULTS: PEF ablation procedures were well tolerated and technically feasible for all 17 of 17 patients. The mean initial size of the target and off-target tumors were 2.6±1.5 cm (range: 0.4 - 6.9cm) and 2.2±1.1 cm (range: 1.0 - 5.2cm), respectively. Overall, 15/30 (50%) target lesions and 12/24 (50%) off-target lesions were unchanged or decreased in size at the patient's last follow-up. Eight patients had overall stable disease (47%) at the last follow-up. There were nine mild (9/26, 35%) and one moderate (1/26, 4%) AE. CONCLUSION: All PEF procedures were technically feasible with one moderate AE and stable disease for 47% of patients with a median follow-up period of three months.

Fracture risk assessment in the presence of competing risk of death.

PURPOSE: To identify the optimal statistical approach for predicting the risk of fragility fractures in the presence of competing event of death. METHODS: We used real-world data from the Dubbo Osteoporosis Epidemiology Study that has monitored 3035 elderly participants for bone health and mortality. Fragility fractures were ascertained radiologically. Mortality was confirmed by the State Registry. We considered four statistical models for predicting fracture risk: (i) conventional Cox's proportional hazard model, (ii) cause-specific model, (iii) Fine-Gray sub-distribution model, and (iv) multistate model. These models were fitted and validated in the development (60% of the original sample) and validation (40%) subsets, respectively. The model performance was assessed by discrimination and calibration analyses. RESULTS: During a median follow-up of 11.3 years (IQR: 7.2, 16.2), 628 individuals (34.5%) in the development cohort fractured, and 630 (34.6%) died without a fracture. Neither the discrimination nor the 5-year prediction performance was significantly different among the models, though the conventional model tended to overestimate fracture risk (calibration-in-the-large index = - 0.24; 95% CI: - 0.43, - 0.06). For 10-year risk prediction, the multistate model (calibration-in-the-large index = - 0.05; 95% CI: - 0.20, 0.10) outperformed the cause-specific (- 0.23; - 0.30, - 0.08), Fine-Gray (- 0.31; - 0.46, - 0.16), and conventional model (- 0.54; - 0.70, - 0.39) which significantly overestimated fracture risk. CONCLUSION: Adjustment for competing risk of death has minimum impact on the short-term prediction of fracture. However, the multistate model yields the most accurate prediction of long-term fracture risk and should be considered for predictive research in the elderly, who are also at high mortality risk. Fracture risk assessment might be compromised by the competing event of death. This study, using real-world data found a multistate model was superior to the current competing risk methods in fracture risk assessment. A multistate model is considered an optimal statistical method for predictive research in the elderly.

Multiple Particle Tracking: A Method for Probing Biologically Relevant Mobility of Bacterial Extracellular Vesicles.

Bacterial extracellular vesicles (bEVs) are produced by both Gram-negative and Gram-positive bacteria. These biological nanoparticles transport small molecules, nucleic acids, and proteins, enabling communication with both bacterial and mammalian cells. bEVs can evade and disrupt biological barriers, and their lipid membranes protect their cargo from degradation, facilitating long-distance communication in vivo. Furthermore, bacteria are easily manipulated and easily cultured. These combined factors make bEVs an ideal candidate for drug delivery applications. Thus, the study of how bEVs interact with biological barriers is interesting from both a signaling and drug delivery perspective. Here we describe methods for tracking bEV motion in biological matrices ex vivo. We outline methods for growth, isolation, quantification, and labeling, as well as techniques for tracking bEV motion ex vivo and quantifying these data. The methods described here are relevant to bEV communication with host cells as well as drug delivery applications using bEVs.

Modeling and characterization of gas coupled ultrasonic transducers at low pressures and temperatures and implications for sonic anemometry on Mars.

A sonic anemometer targeted at wind speed measurements on the surface of Mars is described. This environment requires transducer operation in 4-10 mbar CO2 at temperatures between 143 and 293 K (-130 °C and 20 °C, respectively). Over these ranges, transducer pressure and temperature sensitivity could be a source of measurement error. To investigate this, four candidate transducers were tested using transmission mode ultrasonic testing and impedance measurements: two narrowband piezoelectric transducers, a broadband capacitive transducer, and a micromachined capacitive ultrasound transducer. A system model was used for comparison and interpretation, and implications for a sonic anemometer were examined. Variation of transducer characteristics, including diffraction effects, across 2-10 mbar in CO2 and 190-293 K (-83 °C-20 °C) result in ±2.3% error in wind speed measurement and ±1.1% error in speed of sound measurement for the worst case but only ±0.14% error in wind and ±0.07% error in speed of sound for the best transducer operated off resonance. The acoustic conditions on Mars are similar to those in Earth's stratosphere at 30-42 km of altitude. Hence, testing was also conducted in dry air over the same range of pressures and temperatures with relevance to a secondary application of the instrument as a stratospheric anemometer for high altitude balloon missions on Earth.

Effects of Dapagliflozin in Patients with Membranous Nephropathy.

Introduction: Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial. Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR. Results: Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m2, and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event. Conclusion: In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing.